Diabetes mellitus is a debilitating metabolic disease caused by the absence of insulin production (type 1), or insulin resistance or insufficient insulin production (type 2) from pancreatic β-cells, endocrine cells that manufacture and store insulin for release following a meal. High blood glucose levels stimulate the secretion of insulin by pancreatic β-cells. Insulin, in turn, stimulates the entry of glucose into muscles and adipose cells, leading to the storage of glycogen and triglycerides and to the synthesis of proteins. Activation of insulin receptors on various cell types diminishes circulating glucose levels by increasing glucose uptake and utilization, and by reducing hepatic glucose output. Disruptions within this regulatory network can result in diabetes and associated pathologic conditions.
An individual having a glucose metabolism disorder can suffer from hyperglycemia, hyperinsulinemia, and/or glucose intolerance, along with a host of related disorders. For example, insulin resistance, a disorder often associated with aberrant levels of glucose and/or insulin, is characterized by hepatic, fat, and muscle cells losing their ability to respond to normal blood insulin levels. Such glucose metabolism disorders adversely affect a large and growing number of individuals throughout the world.
Obesity, which is most commonly caused by excessive food intake coupled with limited energy expenditure and/or lack of physical exercise, often accompanies various glucose metabolism disorders. Obesity increases the likelihood of an individual developing various diseases, such as diabetes mellitus, hypertension, atherosclerosis, coronary artery disease, gout, rheumatism and arthritis. Moreover, mortality risk directly correlates with obesity, such that, for example, a body-mass index in excess of 40 results in an average decreased life expectancy of more than 10 years.
Certain pharmacological treatment modalities have demonstrated, to varying degrees, both glucose homeostatic and anti-obesity activity. Unfortunately, such modalities are frequently associated with serious and often debilitating adverse effects.
In view of the prevalence and severity of diabetes, obesity, and associated metabolic and non-metabolic disorders, along with the shortcomings of current treatment options, alternative treatment modalities are needed.